Example of delirium check-list



High-Alert Medications and Suspected Delirium

Background information and research related to these tables:

• A wide range of medications and medication issues may contribute to delirium

o Inappropriate dosing

▪ Too high- for example: digoxin toxicity

▪ Too low- for example: uncontrolled pain may lead to delirium

o Drug-drug interactions

o Drug-disease interactions[i]

▪ Studies demonstrate increase risk in cancer patients on opioids

▪ Studies demonstrate delirium risk is decreased in post-surgical patients when pain is control

o Inappropriate drug selection

▪ Increased drug sensitivities in the elderly

• Potential pathophysiology of delirium based on specific neurotransmitters[ii]:

▪ Excess of dopamine

▪ Depletion of acetylcholine

▪ GABA, serotonin, endorphins and glutamate also play a role

• Many medications maybe suspect, but few are consistently associated with the development of delirium.[iii]

o According to one critical review, psychoactive medications appear to be involved in delirium cases in 15-75% of cases

o Drugs were considered a definite cause of delirium in only 2-14% of cases

o Those cited in the critical review include:

▪ Opioids

▪ Corticosteroids

▪ Benzodiazepines

o Other medications mentioned but not consistently cited include:

▪ Anticholinergics

▪ NSAIDs

▪ Chemotherapeutic agents

o There are not many well designed studies examining drug-induced delirium

▪ The studies have conflicting results

▪ The studies vary in regards to design and analysis

▪ Benzodiazepines and antipsychotics noted significant results in a study

▪ Anticholinergics, anticonvulsants, antidepressants, antiemetics, antiparkinsonians, corticosteroids, H-2 antagonists, and NSAIDs were not significantly associated with delirium in any study noted in the critical review

▪ These studies lack defined controls and numerous variables; therefore, results may not reliably be compared to infer significant findings.

o Critical review conclusions: the currently available epidemiologic evidence of an association of psychoactive medications and delirium is rather weak.

High risk medications specific to the elderly (The Beers Criteria):

• Why the Beers Criteria is important[iv]

o The Beers criteria are based on expert consensus developed through extensive literature reviews identifying medications that may potentially inappropriate in older adults

o Centers for Medicare and Medicaid (CMS) adopted the Beers Criteria in July 1999 for nursing home regulation.

o Studies examining the use of medications found on the list indicate increased provider/facility costs and increased inpatient, outpatient and emergency visits.

o The Beers Criteria was last update via an expert panel examining current literature and professional surveys in 2002

Information about this table- Medications Implicated in Drug-Induced Delirium i

• This in not an all encompassing list; these are medications consistently mentioned in delirium literature

• Just because a patient may be on one or more of these meds, it does not mean it is the absolute cause of delirium

• Medication sensitivity and effect vary greatly from patient to patient, and delirium cases should encompass the patient’s entire medical picture (disease condition, environment, medications, etc.)

Table A- Medications Implicated in Drug-Induced Delirium

|Medication Class |Medication |

|Benzodiazepines | |

| |Lorazepam |

| |Diazepam |

| |Clonazepam |

| |Alprazolam |

| |Triazolam |

| |Clorazepate |

| | |

|Opioids | |

| |Fentanyl * |

| |Meperidine * |

| |Morphine * |

|Corticosteroids | |

| |Prednisone |

| | |

|NSAIDs | |

| |Diclofenac |

| |Ibuprofen |

| |Sulindac |

| |Indomethacin |

| |Salicylic acid |

| |Ketoprofen |

| | |

|Antipsychotics | |

| |Clozapine * ( |

| |Fluphenazine |

| |Haloperidol |

| |Loxapine |

| |Olanzapine ( |

| |Perphenazine |

| |Quetiapine ( |

| |Risperidone |

| |Thioridazine ( |

| |Ziprasidone |

| | |

|Antiarrhythmics | |

| |Amiodarone |

| |Lidocaine |

| |Quinidine |

| |Tocainide |

| | |

|Antiasthmatics | |

| |Theophylline |

| | |

|Anticonvulsants | |

| |Phenytoin |

| |Acetazolamide |

| |Lamotrigine |

| |Pregabalin |

| |Valproic Acid* |

|Medication Class |Medication |

|Antidepressants | |

| |Amitriptyline ( |

| |Desipramine ( |

| |Doxepin ( |

| |Imipramine ( |

| |Protriptyline ( |

| |Mirtazapine ( |

| |Fluoxetine |

| |Paroxetine |

| |Sertraline |

| | |

|Dopaminergic Agents | |

| |Amantadine |

| |Levodpa |

| |Bromocriptine |

| | |

|Antihypertensives | |

| |Enalapril |

| |Captopril |

| |Lisinopril |

| |Reserpine |

| |Clonidine |

| |Methyldopa |

| |Nifedipine |

| |Verapamil |

| |Atenolol |

| |Metoprolol |

| |Propranolol |

| | |

|Anticholinergics | |

| |Atropine ( |

| |Benztropine ( |

| |Scopolamine ( |

| |Tolterodine ( |

| | |

|Antimicrobials | |

| |Tobramycin |

| |Bactrim |

| |Linezolid |

| | |

|Other Agents | |

| |Digoxin |

| |Alcohol withdrawl |

| |Lithium * |

|* Documented incidence from clinical trials |

|( Medications that have anticholinergic effects which can be |

|associated with cognitive impairment |

| |

The Beer’s Criteria and fairly commonly medications iv,[v]

|Drug |Concern |Severity Rating |

|Propoxyphene and combinations |Demonstrates analgesic effects similar to |Low |

| |acetaminophen with adverse effects of narcotics| |

|Indomethacin |Produces most CNS effects of the NSAID class |High |

|Pentazocine |Narcotic with several CNS effects: confusion |High |

| |and hallucinations | |

|Trimethobenzamide |Poor antiemetic effects; potential for EPS |High |

|Muscles relaxants and antispasmodics |Poorly tolerated in elderly; anticholinergic |High |

| |effects; increase fall risk | |

|Flurazepam |Extremely long half-life cause prolonged side |High |

| |effects of sedation and falls | |

|Amitriptyline |Potent anticholinergic; sedating |High |

|Doxepine |Potent anticholinergic; sedating | |

|Meprobamate |Highly addictive anxiolytic |High |

|Specific dosing of benzodiazepines |Doses ranging higher than those suggested |High |

|Lorazepam > 3 mg |demonstrate little benefit with increased side | |

|Oxazepam > 60 mg |effects compared to smaller doses | |

|Alprazolam > 2 mg | | |

|Temazepam > 15 mg | | |

|Triazolam > 0.25 mg | | |

|Long-acting benzodiazepines |Long half-life produces prolonged sedation and |High |

|Chlordiazepoxide |increased risk for falls | |

|Diazepam | | |

|Quazepam | | |

|Halazepam | | |

|Chlorazepate | | |

|Disopyramide |Particular antiarrhythmic may induce heart |High |

| |failure in elderly; also anticholinergic | |

| |effects | |

|Digoxin |Closely monitor renal clearance and levels to |Low |

| |prevent toxicity | |

|Short-acting dipyridamole |Potential for orthostatic hypotenstion; |Low |

| |long-acting formulation only in those with | |

| |prosthetic heart valves | |

|Methyldopa |Bradycardia; may potentiate depression |High |

|Reserpine > 0.25 mg |May induce depression, impotence, sedation, |Low |

| |orthostatic hypotension | |

|Chlorpropamide |Long half-life may prolong hypoglycemia |High |

|GI antispasmodics |Increased anticholinergic effects; efficacy |High |

|Dicyclomine |uncertain | |

|Hyoscyamine | | |

|Belladonna alkaloids | | |

|Clidinium-chlordiazapoxide | | |

|Anticholinergics/Antihistamines |Potent anticholinergic |High |

|Chlorpheniarmine | | |

|Diphenhydramine | | |

|Hydroxyzine | | |

|Cyproheptadine | | |

|Promethazine | | |

|Diphenhydramine |Confusion and sedation; use lowest possible |High |

| |dose in allergic reactions | |

|Ferrous Sulfate > 325 mg/day |High doses not dramatically absorbed; |Low |

| |constipation greatly increased | |

|Barbiturates (except Phenobarbital) |Highly addictive; harmful side effects |High |

|Meperidine |Advantage over other analgesics questionable; |High |

| |increased side effects | |

|Ticlopide |No more efficacious than aspirin for clots; |High |

| |more side effects | |

|Ketorolac |Use (especially long-term) associated with GI |High |

| |side effects | |

|Amphetamines |Addictive; Induce hypertension, angina, and |High |

| |myocardial infarction | |

|Long-term use of NSAIDs |GI bleeds, renal failure, high blood pressure, |High |

| |heart failure | |

|Bisacodyl |Long-term use may exacerbate bowel dysfunction |High |

|Amiodarone |May prolong QT interval; questionable efficacy |High |

| |in elderly | |

|Fluoxetine (daily dosing) |Long half-life may prolong CNS stimulation, |High |

| |sleep disturbances, agitation | |

|Nitrofurantoin |Renal impairment |High |

|Doxazosin |Hypotention; anticholinergic effects |Low |

|Methyltestosterone |Prostatic hypertrophy; cardiac issues |High |

|Short acting nifedipine |Hypotension; constipation |High |

|Clonidine |Hypotension; CNS effects |Low |

|Mineral oil |Risk for aspiration and other side effects |High |

|Cimitidine |Increased CNS effects (confusion); drug |Low |

| |interactions | |

|Ethacrynic acid |Hypertension; fluid imbalances |Low |

|Estrogens only agents |Evidence of carcinogenic potential and lack of |Low |

| |cardio-protective effects in elderly women | |

|Notes: |

|Abbreviations: CNS- central nervous system; NSAIDs- nonsteroidal anti-inflammatory drugs; EPS- extrapyramidal symptoms |

|Anticholinergic effects- may effect several different systems; most notable effects include: ataxia, dry mouth and eyes, blurred vision, |

|constipation, tachycardia, light-headedness urinary retention, confusion, and agitation. |

| | | |

References:

-----------------------

[i] Borovick and Fuller. Drug-Induced Diseases: Prevention, Detection, and Management: 2nd ed. ASHP 2010; Chapter 15: Delirium.

[ii] Girard TD, et al. Crit Care 2008; 12(Suppl 3): S3

[iii] Gaudreau JD, et al. Psychosomatics 2005; 46(6): 302-316

[iv] Fick DM, et al. Arch Intern Med 2003; 163: 2716-2724

[v] PA-PSRS Patient Safety Advisory 2005; Vol 2(4)

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